Dissertation
Enhancing the immunogenicity of anti-HIV DNA vaccines with molecular adjuvants
Doctor of Philosophy (Ph.D.), Drexel University
Jul 2019
DOI:
https://doi.org/10.17918/3wxw-dj93
Abstract
Almost two million people are infected with HIV-1 annually, highlighting the need for an effective prophylactic vaccine. Two important challenges facing the design of successful HIV-1 prophylactic vaccines are that an effective HIV vaccine must (1) induce high titers of broadly neutralizing antibodies (bNAbs) and (2) must direct the bulk of these humoral responses to mucosal surfaces, the primary sites of HIV sexual transmission. In these studies, we evaluate the immunogenicity of HIV-1 envelope (env) DNA immunogens when co-delivered with plasmid-encoded, or molecular, adjuvants. In order to direct vaccine-induced responses to the mucosa we co-immunized animals with DNA plasmids encoding env and the mucosa-associated epithelial chemokine (MEC; CCL28), which directs IgA-secreting B cells to mucosal surfaces. Animals co-immunized with plasmid-encoded MEC (pMEC) had increased HIV-specific IgA at mucosal surfaces, demonstrating that MEC can be used to direct HIV vaccine-induced humoral responses to mucosal surfaces. We focused on the germinal center (GC) to address the difficulty in generating HIV-1 neutralizing antibodies with vaccination. We hypothesized that co-immunization with molecular ADA (pADA), which supports T cell help, would enhance HIV-specific antibody responses in mice. pADA co-immunized animals displayed increased HIV-specific IgG in serum, and frequencies of TFH in the draining-lymph nodes. When combined with protein co-immunization, pADA immunization supported neutralizing antibody formation. These studies demonstrate that molecular adjuvants can be used to target specific immunological compartments. These results will not only inform the design of HIV vaccines but have broader implications for any vaccine target where site-specific immunity is required.
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Details
- Title
- Enhancing the immunogenicity of anti-HIV DNA vaccines with molecular adjuvants
- Creators
- Ebony Nicole Gary - DU
- Contributors
- Michele Kutzler (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- iii, 224 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 9948; 991014632402904721